STAT6, NF- Kappa B and C/EBP in CD23 expression and IgE production

• Published in: International immunology 1998, Vol.10 (10), p.1529-1538
• Main Authors: Tinnell, S B, Jacobs-Helber, S M, Sterneck, E, Sawyer, ST, Conrad, D H
• Format: Article
• Language: English
• ISSN: 0953-8178
• DOI: 10.1093/intimm/10.10.1529

STAT6, NF- Kappa B (p50) and C/EBP beta transcription factors (TF) were examined with respect to CD23 regulation. Electrophoretic mobility shift assay (EMSA), competition and supershift analysis demonstrated that STAT6 binds the CD23a promoter but with a lower affinity than the consensus site. STAT6 super(-/-) mice were analyzed for CD23 levels and showed reduced expression after CD40 ligand trimer (CD40LT) stimulation. However, normal CD23 expression and even some IgE production was induced in STAT6 super(-/-) mice with CD40LT/IL-4. EMSA analysis indicated that the CD23a STAT site was bound by a protein in nuclear extracts from CD40 plus or minus IL-4-stimulated STAT6 super(-/-) B cells. Western blot analysis of these nuclear extracts demonstrated the presence of STAT3 and STAT5, suggesting that these STATs can induce CD23 in this situation. Further supporting evidence was obtained by showing that IL-2 and IL-4 both synergize with CD40 in an identical manner for CD23 induction on STAT6 super(-/-) B cells. EMSA analysis of the two putative NF- Kappa B sites confirmed binding to both, although one site bound with a higher affinity than the second. Analysis of p50 super(-/-) mice indicated that this subunit was not necessary for CD23 induction or CD40/IL-4-induced IgE production. Finally, no role for C/EBP was observed in CD23 induction by EMSA or by CD23 induction analysis in C/EBP beta super(-/-) mice, whereas the absence of C/EBP beta did have an effect on IgE production and lipopolysaccharide-induced B cell proliferation. Based on these data, a model is presented which suggests that CD23 superinduction results from STAT and NF- Kappa B interaction.